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Heavy metals cause deleterious effects on human health and drastically alter the biogeochemical cycles within freshwater habitats. The main human activities leading to heavy metal contamination of various aquatic ecosystems comprise the industry, agriculture, urbanization, transport and mining. Lake Nasser is the main freshwater source in Egypt, usually polluted from upstream human activities from the hydrographic basin of the River Nile. The current study surveyed the impact of heavy metals contamination (i.e., Cd, Zn, Pb and Cu) in water, sediment and two Nile Tilapia (Oreochromis niloticus) fish organs (liver and muscles) at six sampling sites along Lake Nasser. Additionally, the effects of heavy metals bioaccumulation in the aquatic ecosystem, via water, sediments and fish organs were investigated. The conclusion is that the water of Lake Nasser is safe for use in terms of human consumption, agricultural utilization and public sanitation.